The 2022 Penn Medicine Information Services Benefits Realization report reviews thirty-two (32) high-profile, high-quality projects implemented in fiscal years 2020 and 2021. The Penn Medicine Information Services (IS) team collaborated with operational and clinical partners to generate substantial financial and qualitative benefits in this year’s report. The projects are grouped into five categories that define key strategic goals of Penn Medicine: Empowering Technologies, Digital Healthcare, Making Data Meaningful, Making the Connection, and Research. In this edition, there is also a COVID-19 Section which describes extraordinary collaboration between IS and the Penn Medicine clinical and operational leaders in responding to the worldwide pandemic. In addition, there is a look ahead - spotlighting the multiple projects that were completed in support of the University of Pennsylvania - Pavilion launch in the fall of 2021.